Nicorette, Commit lozenge and NicoDerm CQ cancer scares

Researchers have long known that NNN (N-Nitrosonornicotine) is a potent cancer causing chemical in animals. They know that nicotine is converted into nornicotine as tobacco ages, and that the curing and storage process somehow transforms nornicotine into the deadly carcinogen NNN. They know that additional NNN is created when tobacco is burned and inhaled by smokers. But imagine their horror upon discovering levels of NNN in the urine of nicotine gum and lozenge users that were 7, 31, 36 and 728 times higher than when smoking.

An October 2009 study published in the online version of Cancer Research found that urine NNN levels in 13 of 34 participants in two nicotine gum or lozenge studies were at times equal or greater than background urine NNN levels recorded while still smoking.

The below chart shows measurement of NNN in the urine of eight oral nicotine users in one portion of the study (POB data - see bottom of Table S1). Except for day 3, a week or more passed between urine samples. NNN's half-life inside the body is roughly three hours (184 minutes). NNN's three hour half-life means that within 24 hours more than than 99% of NNN can be eliminated from the body. Sampling urine just once in seven days, clearly, the below chart leaves gaping holes in our understanding of how high NNN spikes can actually rise and how frequently they occur.

Total NNN urine levels in 8 POB study subjects as measured in pmol/24h at both baseline while still smoking and on specific days after quitting smoking while using oral nicotine (nicotine gum or lozenge)

Gum or Lozenge User

Baseline

Day 3

Day 7

Day 14

Day 21

Day 28

Day 42

Day 56

Oral NRT User #1

67

219

-

256

622

578

253

130

Oral NRT User #2

81.5

88

59,400

1,250

11

558

6.8

118

Oral NRT User #3

15

3.9

0.3

0.2

0.3

473

0.3

0.2

Oral NRT User #4

6.5

3.2

2.7

0.2

0.3

0.3

2.9

0.3

Oral NRT User #5

329

14

359

32

16

14

18

3.7

Oral NRT User #6

665

17,900

103

18,200

3,310

23,900

4,080

8.7

Oral NRT User #7

8.7

64

1.4

0.5

0.07

0.06

.015

.016

Oral NRT User #8

4.4

0.1

0.1

0.1

0.06

0.1

0.1

0.17

We've known for a decade that applying NNN twice weekly for 28 weeks inside the nasal cavity of three month-old minks required an average of 97 weeks before resulting cancerous tumors invaded the mink's brain (1999 Koppang). What we don't know after 25 years of nicotine gum being on the market is whether or not long-term use of nicotine replacement therapy (NRT) causes cancer.

NNN's primary path of harm in mice, rats and hamsters is development of cancer in the esophagus, trachea and nasal passages (1992 Kopping). But what about humans? Do massive NNN urine spikes suggest concerns about kidney or bladder cancer?

"In my opinion, the most likely cancers to be associated with long
term NRT use would be lung and upper aero-digestive tract. But we do
not have sufficient epidemiologic data on either" says Stephen S. Hecht, Ph.D, a University of Minnesota cancer prevention professor and researcher, and a co-author of the Cancer Research study.

The U.S. Food and Drug Administration (FDA) first approved prescription nicotine gum in 1984. Today, roughly 40% of Nicorette users are hooked on the cure. President Obama is believed to be among them. Why has it taken a quarter of a century for researchers to realize that NNN spikes in the urine of oral nicotine users can be up to 700 times higher than when smoking?

"Only relatively recently have we developed a method for measurement of NNN in human urine," says Professor Hecht.

Professor Hecht assisted Professor Irina Stepanov, also of the University of Minnesota, in developing a process for measuring tobacco nitrosamines, including NNN. They co-authored an April 2005 paper in Cancer Epidemiology, Biomarkers & Prevention. It found that the mean level of NNN in the urine of 14 smokers was 0.18 pmol/mg, while the level in 11 smokeless tobacco users was 3.5 times higher at 0.64.

But doesn't an NNN urine finding of 59,400 pmol over 24 hours mean that long-term use of oral forms of NRT is unsafe?

"I do not think there are sufficient studies to assess the effects
of long term NRT use - safe or unsafe," says Professor Hecht. "NRT is safer than smoking because it does not involve exposure to multiple other toxicants and carcinogens. But our study raises some concerns about NRT use which should be addressed by the manufacturers of these products."

How does the human body transform nicotine into nornicotine and then NNN?
Does the e-cigarette's nicotine vapor mist cause massive NNN urine spikes too, or like the transdermal nicotine patch (which the October study also evaluated), will spikes be far less frequent and vastly less profound? And why does the method of nicotine delivery affect NNN levels? We're left with vastly more questions than answers.

Nitrosation is a process of converting organic compounds into nitroso derivatives. According to Professor Hecht, "There are many factors which can influence nitrosation by generating relatively high levels of nitrite in the acidic environment of the stomach, together with nornicotine. These could include diet, infections, and others."

Still, today, we do not know which oral NRT users will experience massive NNN spikes, what causes them, how high the spikes will go, how frequently they'll occur, whether they will cause cancer, and if so, where in the body cancer will result.

October 20, 2009 PLoS One Nicotine Study - Not only is nicotine transformed via nornicotine into the potent carcinogen NNN, nicotine itself promotes cancer. It does so by preventing diseased cells from dying (a natural process known as apoptosis) and by actually forming new blood vessels that nourish and feed tumors (angiogenesis). Now, for the first time, a study suggests the gravity of nicotine use while having a tumor.

A free online study in PLoS One found that mice wearing NicoDerm CQ patches experienced a 64% increase in the size of implanted tumors, over tumors in mice not wearing the patch. Nicotine's tumor growth effects were even greater in mice receiving injections of nicotine, where tumors were 3.2 times larger. What we don't yet know is whether nicotine's impact on tumor grow rates in humans will be similar to rates seen in mice.

"Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%)" as compared to mice not receiving nicotine (19.5%). Nicotine also increased metastasis by 9 fold (900%), as measured by the rate by which cancer cells traveled from the flank or hind-end of mice (the tumor implant site) to their lungs.

"While nicotine has been demonstrated to induce cell proliferation, angiogenesis and growth of tumors, the studies presented here show for the first time that nicotine patches can promote tumor re-growth and metastasis," writes the study's authors. "Our results also show that a commercially available nicotine transdermal patch can promote the growth of tumors implanted into mice."

NRT Risk-Benefit Analysis - What neither paper mentions is NRT's lack of value as a smoking cessation aid, its real-world failure to prevail over those attempting to quit without it. Clearly, NRT is generally twice as effective as placebo controls inside randomized clinical trials. What's equally clear is that NRT trials were not blind as claimed, that 3-4 times as many placebo group members correctly guess their group assignment as guess wrong. It may be impossible to hide the onset of full-blown nicotine withdrawal from smokers with lengthy quitting histories, smokers skilled at recognizing it.

Simon Chapman, Ph.D, is a public health professor at the University of Sidney and recently retired editor of the journal Tobacco Control. On September 18, 2009 he wrote, "For years, cold turkey has been denigrated as a hopeless strategy and ignored in public campaigns. But ask 1000 ex-smokers how they stopped and you get a very different answer." "[P]opulation studies consistently have shown that a large majority of smokers who permanently succeed in quitting do not use any form of assistance."

Professor Siegel closes by asserting, "In light of these 10 problems, I believe that it is time for a serious re-examination of both the effectiveness of nicotine replacement therapy and the role of NRT as part of a national strategy for the promotion of smoking cessation."

Far too many pharmaceutical industry salesman have been allowed to masquerade for far too long as university cessation pharmacology research scientists. If addicted and alive, feel good not bad. Although a quarter of a century late, when hundreds of thousands should still be alive, science's cavalry (as shown by the above safety and effectiveness studies) is beginning to arrive.

How to quit smoking

Our free quitting e-books

Read both & demolish quitting anxieties!

Learn More About Smart Turkey Quitting

WhyQuit.com - WhyQuit is the Internet's oldest forum devoted to the art, science and psychology of cold turkey quitting, the stop smoking method used by the vast majority of all successful long-term ex-smokers. Left to right, WhyQuit is organized under three headings: (1) Motivation, (2) Education and (3) Support.

"Never Take Another Puff" - Imagine a free 149 page stop smoking ebook that's registered more than 4 million downloads and was written by a man who has devoted 40 years, full-time to helping smokers quit. Never Take Another Puff (NTAP) was authored by Joel Spitzer, the Internet's leading authority on how to stop smoking cold turkey. It is an insightful collection of almost 100 articles on every cessation topic imaginable.

"Freedom from Nicotine - The Journey Home" - Written by John R. Polito, a former 30-year heavy smoker and WhyQuit's 1999 founder, Freedom from Nicotine (FFN) is a free nicotine dependency recovery book that documents the science underlying nicotine dependency and successful cessation. Whether hooked on cigarettes, e-cigarettes (e-cigs), bidis, kreteks, a pipe, hookah or cigars, on dip, chew, snuff or snus, or on the nicotine gum, lozenge, spray, inhaler or patch, FFN provides a comprehensive yet easy to follow road-map to freedom from nicotine.

Turkeyville - Visit Turkeyville, Facebook's most popular quit smoking support group. The group's primary focus is the first few days and helping new quitters get started. Yes you can!

Joel's Library - Joel's Library is home to Joel Spitzer's "Daily Quitting Lesson Guide." The Guide walks new quitters through the first two weeks of smoking cessation, recommending daily videos to watch and articles to read. Joel's Library is also home to more than 100 original short stop smoking articles, to his free ebook Never Take Another Puff, and to his collection of more than 200 video stop smoking lessons.

Freedom - Looking for a deadly serious and highly focused education oriented support group? Home to Joel Spitzer, Freedom is the Internet's only 100% nicotine-free peer messageboard support forum. Explore Freedom's hundreds of thousands of archived member posts on how to quit smoking.